RESUMO
Introduction: Due to the increase in the number of early-stage breast cancer patients, there is growing interest in minimally invasive local therapies for breast cancer. Radiofrequency ablation (RFA) therapy is one of the most promising minimally invasive treatments. The Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (RAFAELO) study, a multicenter collaborative study that aims to validate the efficacy and safety of RFA and to standardize its use for early-stage breast cancer, was conducted under the Advanced Medical Care B system in 2013. This study enrolled the expected number of patients in November 2017; moreover, it is currently in the follow-up period. Some patients with early-stage breast cancer who are eligible for RFA could not receive the RFA treatment, as it is still not covered by insurance. Therefore, the Patients Offer Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (PO-RAFAELO) study under the Patient-proposed Health Services (PPHS) was proposed and approved in March 2019. Methods: The PPHS is a system that allows patients to receive prompt access to advanced medical care at a medical facility close to them, starting with their request. This system is considered a part of the specific and special medical coverage. The PO-RAFAELO study is the only study in the surgical field utilizing the PPHS, aiming to help in achieving regulatory approval and insurance coverage of RFA for breast cancer. Results: As of January 2023, 120 patients have undergone RFA using the PPHS and no grade 3 or higher early adverse events have occurred. Conclusions: A certain number of patients with early-stage breast cancer prefer nonsurgical treatment, and it is important to provide information regarding the availability of RFA for early-stage breast cancer under the PPHS.Trial registration: registered with Japan Registry of Clinical Trial on March 06, 2019 (Trial ID: jRCTs032180187).
RESUMO
Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1-3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 ≥ 20%. Cohort 3 comprised patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 < 20%. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) between HER2-low (IHC1+ or IHC2+/FISH-) and HER2-zero (IHC0) groups in each cohort. In cohort 1, HER2-low patients exhibited significantly better 5-year IDFS (84.2% vs. 73.6%, p = 0.0213) and DRFS (88.2% vs. 79.8%, p = 0.0154). However, no significant differences were observed in cohorts 2 and 3. Our findings suggest HER2-low positivity as a prognostic factor in HR-positive, HER2-negative, and node-positive EBC.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Antígeno Ki-67 , Estudos Retrospectivos , Recidiva Local de Neoplasia , Receptor ErbB-2/metabolismoRESUMO
Human epidermal growth factor receptor 2 (HER2) protein, which is characterized by the amplification of ERBB2, is a molecular target for HER2-overexpressing breast cancer. Many targeted HER2 strategies have been well developed thus far. Furthermore, intratumoral heterogeneity in HER2 cases has been observed with immunohistochemical staining and has been considered one of the reasons for drug resistance. Therefore, we conducted an integrated analysis of the breast cancer single-cell gene expression data for HER2-positive breast cancer cases from both scRNA-seq data from public datasets and data from our cohort and compared them with those for luminal breast cancer datasets. In our results, heterogeneous distribution of the expression of breast cancer-related genes (ESR1, PGR, ERBB2, and MKI67) was observed. Various gene expression levels differed at the single-cell level between the ERBB2-high group and ERBB2-low group. Moreover, molecular functions and ERBB2 expression levels differed between estrogen receptor (ER)-positive and ER-negative HER2 cases. Additionally, the gene expression levels of typical breast cancer-, CSC-, EMT-, and metastasis-related markers were also different across each patient. These results suggest that diversity in gene expression could occur not only in the presence of ERBB2 expression and ER status but also in the molecular characteristics of each patient.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Sequência de Bases , Análise de Sequência de RNA , Análise de Célula Única , Coloração e RotulagemRESUMO
PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.
RESUMO
AIMS: SP142 and 22C3 assays are approved companion diagnostic assays for anti-PD-1/PD-L1 therapy selection in metastatic triple-negative breast cancer (TNBC). The discordance in PD-L1 status between primary and metastatic tumors in the same patient has been poorly characterized. Here, we examined the concordance of PD-L1 status between the two assays and between primary tumors and metastases for each assay. METHODS: We retrospectively evaluated tumor samples from 160 patients with TNBC, including 45 patients with paired primary and metastatic tumors. PD-L1 status was assessed using SP142 and 22C3 assays, to determine the immune cell (IC) score, tumor cell (TC) score (SP142 and 22C3), and combined proportion score (CPS: 22C3). RESULTS: The concordance of PD-L1 positivity at diagnostic cutoffs for SP142 (IC ≥ 1) and 22C3 (CPS ≥ 10) was substantial (κ = 0.80) in primary tumors and moderate (κ = 0.60) in metastatic tumors. In comparison, between primary and metastatic tumors, the concordance with 22C3 was moderate (κ = 0.50), whereas that with SP142 was poor (κ = -0.03). Among patients who were PD-L1 negative for both assays in primary tumors, 7/30 (23.3%) were PD-L1 positive for both or either 22C3 or SP142 in the metastatic tumors. CONCLUSIONS: The inter-assay concordance of PD-L1 positivity at diagnostic cutoffs was substantial in primary tumors and moderate in metastatic tumors. Discordance between PD-L1 status in primary and metastatic tumors was frequently observed, especially with SP142. Some patients with a PD-L1-negative status in primary tumors may still be candidates for immunotherapy, depending on the PD-L1 status in their metastatic tumors.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico , Imuno-Histoquímica , Estudos Retrospectivos , Antígeno B7-H1/metabolismo , Imunoterapia , Biomarcadores TumoraisRESUMO
BACKGROUND: Histological grade (HG) has been used in the MonrachE trial to select patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive high-risk early breast cancer (EBC). Although nuclear grade (NG) is widely used in Japan, it is still unclear whether replacing HG with NG can appropriately select high-risk patients. METHODS: We retrospectively reviewed 647 patients with HR-positive, HER2-negative, node-positive EBC and classified them into the following four groups: group 1: ≥ 4 positive axillary lymph nodes (pALNs) or 1-3 pALNs and either grade 3 of both grading systems or tumors ≥ 5 cm; group 2: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 ≥ 20%; group 3: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 < 20%; and group 4: group 2 or 3 by HG classification but group 1 by NG classification. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) among the four groups using the Kaplan-Meier method with the log-rank test. RESULTS: Group 1 had a significantly worse 5-year IDFS and DRFS than groups 2 and 3 (IDFS 80.8% vs. 89.5%, P = 0.0319, 80.8% vs. 95.5%, P = 0.002; DRFS 85.2% vs. 95.3%, P = 0.0025, 85.2% vs. 98.4%, P < 0.001, respectively). Group 4 also had a significantly worse 5-year IDFS (78.0%) and DRFS (83.6%) than groups 2 and 3. CONCLUSIONS: NG was useful for stratifying the risk of recurrence in patients with HR-positive, HER2-negative, node-positive EBC and was the appropriate risk assessment for patient groups not considered high-risk by HG classification.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Antígeno Ki-67/metabolismo , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/metabolismo , Intervalo Livre de DoençaRESUMO
Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.
RESUMO
Introduction: Triple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated. Methods: Herein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy. Results: All patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2- 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58-31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors. Conclusion: For patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population.
RESUMO
PURPOSE: The impact of progesterone receptor (PR) status on the prognosis of breast cancer after isolated locoregional recurrence (ILRR) remains unclear. This study evaluated the impact of clinicopathologic factors, including PR status of ILRR, on distant metastasis (DM) after ILRR. METHODS: We retrospectively identified 306 patients with ILRR diagnosed at the National Cancer Center Hospital between 1993 and 2021 from the database. Cox proportional hazards analysis was performed to examine factors associated with DM after ILRR. We developed a risk prediction model based on the number of detected risk factors and estimated survival curves using the Kaplan-Meier method. RESULTS: During a median follow-up time of 4.7 years after ILRR diagnosis, 86 patients developed DM, and 50 died. Multivariate analysis revealed that seven risk factors were associated with poor distant metastasis-free survival (DMFS): estrogen receptor-positive/PR-negative/human epidermal growth factor receptor 2-negative ILRR, short disease-free interval, recurrence site other than ipsilateral breast, no-resection of ILRR tumor, chemotherapy for the primary tumor, nodal stage in the primary tumor, and no endocrine therapy for ILRR. The predictive model classified patients into 4 groups based on the number of risk factors: low-, intermediate-, high-, and the highest-risk groups with 0 to 1, 2, 3 to 4, and 5 to 7 factors, respectively. This revealed significant variation in DMFS among the groups. A higher number of the risk factors was associated with poorer DMFS. CONCLUSION: Our prediction model, which considered the ILRR receptor status, may contribute to the development of a treatment strategy for ILRR.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND/OBJECTIVE: The occurrence of iatrogenic tumor cell seeding (seeding) in needle tract scars formed by core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) is well known. Some risk factors for seeding have been reported, but the clinicopathological risk factors and its prognosis have not been fully investigated. We evaluated the clinical features and prognosis of seeding. METHODS: We included 4405 patients who had undergone surgery (lumpectomy or mastectomy) with a diagnosis of breast cancer by preoperative CNB or VAB at our hospital between January 2012 and February 2021. Data of patients with confirmed presence of seeding in resected specimens were collected from pathological records. We analyzed the risk factors of seeding using logistic regression analysis and compared the ipsilateral breast tumor recurrence (IBTR) rate between cases based on the presence or absence of seeding in the lumpectomy group. RESULTS: Of the 4405 patients, 133 (3.0%) had confirmed seeding. Univariate analysis revealed the association of clinicopathological features of seeding with lower nuclear grade (NG1 vs NG2-3; p = 0.043), lower Ki-67 (<30 vs. ≥30; p = 0.049), estrogen receptor (ER) positivity (positive vs negative; p<0.01), and human epidermal growth factor receptor 2 (HER2) negativity (negative vs positive; p = 0.016). Multivariate analysis showed ER positivity (odds ratio, 5.23; p<0.05) as an independent risk factor of seeding. The IBTR rate was not significantly different between the seeding and non-seeding groups. CONCLUSIONS: Seeding was more likely to occur in ER positive, HER2 negative carcinomas with less aggressive features, and may remain subclinical if adequate adjuvant treatments are administered.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Relevância Clínica , Mastectomia , Recidiva Local de Neoplasia/patologia , Biópsia com Agulha de Grande Calibre , Doença IatrogênicaRESUMO
PURPOSE: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. METHODS: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin-eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. RESULTS: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57-11.99, p = 0.005). Patients with high CD8/PD-L1 (-) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1( +) tumors had the worst prognosis (5 year iDFS, 33.3%). CONCLUSION: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8-positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.
Assuntos
Estruturas Linfoides Terciárias , Neoplasias de Mama Triplo Negativas , Humanos , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia , Estudos Retrospectivos , Linfócitos do Interstício Tumoral , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estruturas Linfoides Terciárias/patologia , Ligantes , Biomarcadores/metabolismo , Quimioterapia Adjuvante , Linfócitos T CD8-Positivos , ApoptoseRESUMO
BACKGROUND: Chemotherapy and radiotherapy were postulated to induce an inflamed tumour microenvironment. We aimed to evaluate the effects of adjuvant chemotherapy/radiotherapy on tumour-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression in metastatic breast cancer. METHODS: We identified paired primary and metastatic tumours in 85 patients with breast cancer. Stromal TILs were assessed according to international guidelines. PD-L1 expression was evaluated using the VENTANA SP142 assay. RESULTS: TILs were significantly lower in metastatic tumours than in primary tumours (12.2 vs. 8.3%, p = 0.049). PD-L1 positivity was similar between primary and metastatic tumours (21.2 vs. 14.1%, p = 0.23). TILs were significantly lower in patients who received adjuvant chemotherapy than in those who did not (-9.07 vs. 1.19%, p = 0.01). However, radiotherapy had no significant effect on TILs (p = 0.44). Decreased TILs predicted worse post-recurrence survival (hazard ratio, 2.94; 95% confidence interval [CI]: 1.41-6.13, p = 0.003), while increased TILs was associated with a better prognosis (HR, 0.12; 95% CI: 0.02-0.08, p = 0.04). CONCLUSIONS: TILs decreased in metastatic tumours, particularly in patients who relapsed after adjuvant chemotherapy. Changes in TILs from primary to metastatic sites could be a prognostic factor after recurrence.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Antígeno B7-H1/metabolismo , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Quimioterapia Adjuvante , Microambiente TumoralRESUMO
PURPOSE: Male breast cancer (MBC) is a rare cancer accounting for only 1% of all male cancers and is, therefore, poorly studied. We aimed to characterize the subtypes of MBC in Japanese patients based on genetic profiling, the presence of tumor-infiltrating cells, and the expression of immunohistochemical markers. METHODS: This retrospective study included 103 patients with MBC diagnosed between January 2009 and December 2019 at various hospitals in Japan. Clinicopathological patient characteristics were obtained from medical records, and formalin-fixed paraffin-embedded tissue specimens were analyzed for histological markers, mutations of 126 genes, BRCA1 methylation, and stromal tumor-infiltrating lymphocytes. RESULTS: The median patient age was 71 (range 31-92) years. T1-stage tumors were the most frequent (47.6%), and most were node negative (77.7%). The majority of tumors were positive for estrogen receptor (98.1%), progesterone receptor (95.1%), and androgen receptor (96.1%), and BRCA2 was the most frequently mutated gene (12.6%). The most common treatment was surgery (99.0%), either total mastectomy (91.1%) or partial mastectomy (7.0%). Survival analysis showed a 5-year recurrence-free survival rate of 64.4% (95% confidence interval [CI] 46.7-88.8) and a 5-year overall survival rate of 54.3% (95% CI 24.1-100.0). CONCLUSION: Japanese MBC is characterized by a high rate of hormonal receptor positivity and BRCA2 somatic mutation. Due to the observed clinicopathological differences in MBC between the Western countries and Japan, further prospective studies are needed to evaluate the most suitable treatment strategies.
Assuntos
Neoplasias da Mama Masculina , Neoplasias da Mama , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , População do Leste Asiático , Mastectomia , Metilação , Mutação , Estudos RetrospectivosRESUMO
BACKGROUND: /Objective: To evaluate the usefulness of combining radioisotopes (RI) and indocyanine green (ICG) and investigate discordances in sentinel lymph node (SN) reactivity using each tracer in cN0 breast cancer patients. METHODS: In total, 338 cN0 primary breast cancer patients who underwent SN biopsy with RI and ICG and axillary lymph node (ALN) dissection were included. SN positivity with RI, ICG, and a combination of RI and ICG was denoted as SN(RI), SN(ICG), and SN(RI+ICG), respectively. We retrospectively estimated metastatic SN detection rates, each method's discordance rate, and the correlation of discordances in SN reactivity with postoperative N staging. RESULTS: The combination of RI and ICG had higher metastatic SN detection rates (99.7%) than RI or ICG alone (91.7% and 96.4%, respectively; p < 0.01). The discordance rate between SN(RI) and SN(ICG) in detecting metastatic SNs was 11.3% (38/337 cases). The absence of SN(RI), cT stage (cT2-3), higher histological grade (G3), and histological type (special type) were identified as risk factors of pN2-3 disease (odds ratios: 8.64, 2.56, 1.92, and 3.28, respectively; p < 0.01). CONCLUSION: Discordances in SN reactivity between RI and ICG helps in identifying SN metastasis. Although the absence of SN(RI) is rare, it is a significant sign of advanced ALN metastases. The findings of our study indicate that ALN dissection should be considered for accurate nodal staging in such cases.
Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Verde de Indocianina , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Estudos Retrospectivos , Relevância Clínica , Biópsia de Linfonodo Sentinela , Metástase Linfática/patologia , Radioisótopos , Linfonodos/patologiaRESUMO
BACKGROUND: There are currently no scoring-type predictive models using only easily available pre- and intraoperative data developed for assessment of the risk of advanced axillary lymph node metastasis (ALNM) in patients with breast cancer with metastatic sentinel lymph nodes (SLNs). We aimed to develop and validate a scoring system using only pre- and intraoperative data to distinguish between non-advanced (≤ 3 lymph nodes) and advanced (> 3 lymph nodes) ALNM in patients with breast cancer with metastatic SLNs. METHODS: We retrospectively identified 804 patients with breast cancer (cT1-3cN0) who had metastatic SLNs and had undergone axillary lymph node dissection (ALND). We evaluated the risk factors for advanced ALNM using logistic regression analysis and developed and validated a scoring system for the prediction of ALNM using training (n = 501) and validation (n = 303) cohorts, respectively. The predictive performance was assessed using the receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration plots. RESULTS: Ultrasound findings of multiple suspicious lymph nodes, SLN macrometastasis, the ratio of metastatic SLNs to the total number of SLNs removed, and the number of metastatic SLNs were significant risk factors for advanced ALNM. Clinical tumor size and invasive lobular carcinoma were of borderline significance. The scoring system based on these six variables yielded high AUCs (0.90 [training] and 0.89 [validation]). The calibration plots of frequency compared to the predicted probability showed slopes of 1.00 (training) and 0.85 (validation), with goodness-of-fit for the model. When the cutoff score was set at 4, the negative predictive values (NPVs) of excluding patients with advanced ALNM were 96.8% (training) and 96.9% (validation). The AUC for predicting advanced ALNM using our scoring system was significantly higher than that predicted by a single independent predictor, such as the number of positive SLNs or the proportion of positive SLNs. Similarly, our scoring system also showed good discrimination and calibration ability when the analysis was restricted to patients with one or two SLN metastases. CONCLUSION: Our easy-to-use scoring system can exclude advanced ALNM with high NPVs. It may contribute to reducing the risk of undertreatment with adjuvant therapies in patients with metastatic SLNs, even if ALND is omitted.
Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Segunda Neoplasia Primária/cirurgia , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo SentinelaRESUMO
Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) has become widespread worldwide, the problem of inter-observer variability remains. To maintain uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI-RADS3 or lower or BI-RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep-learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI-RADS3 or lower and BI-RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.
Assuntos
Neoplasias da Mama , Aprendizado Profundo , Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Sensibilidade e Especificidade , Ultrassonografia , Ultrassonografia Mamária/métodosRESUMO
Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC. SIGNIFICANCE: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Biomarcadores , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Perfilação da Expressão Gênica , HumanosRESUMO
PURPOSE: We aimed to examine whether cardiorespiratory fitness and leg strength can be estimated based on their relationship with physical performance tests in Japanese breast cancer survivors. METHODS: Participants were 50 sedentary women aged 20 to 59 years who have received breast surgery in the past 2 to 13 months after diagnosis of invasive breast cancer (stage I-IIa). Cardiorespiratory fitness and leg strength were measured by peak oxygen consumption (VO2peak), and one-repetition maximum for leg press (leg press 1RM). Physical performance tests were performed 6-min walk test, chair stand test, and grip strength. Using multiple regression analysis, we developed prediction equations for VO2peak and leg strength based on their associations with the physical performance tests. The validity of the estimation equations was assessed using Bland-Altman plots. RESULTS: Mean age, VO2peak, and leg press 1RM were 48 ± 6 years, 25.0 ± 3.6 mL/kg/min, and 95 ± 32 kg, respectively. Multiple regression analysis yielded 6-min walk test distance, age, height, and body weight as predictors of VO2peak. Measured VO2peak and predicted VO2peak showed a moderate positive correlation (r = 0.463, p < 0.001). Chair stand test, grip strength, age, height, and body weight were selected as predictors of leg press 1RM. There was a strong positive correlation between predicted and measured leg press 1RM (r = 0.754, p < 0.001). CONCLUSION: The results suggest that leg strength can be predicted using physical performance tests. However, further examination may be needed to determine whether cardiorespiratory fitness can be predicted based on 6-min walk test.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Aptidão Cardiorrespiratória , Adulto , Aptidão Cardiorrespiratória/fisiologia , Teste de Esforço/métodos , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Força Muscular/fisiologia , Consumo de Oxigênio/fisiologia , Aptidão Física , Adulto JovemRESUMO
Clinical response predictions through image examinations after neoadjuvant chemotherapy (NAC) for breast cancer is important. The present study aimed to evaluate the utility of a novel imaging modality, positron-emission tomography/magnetic resonance imaging (PET/MRI), in predicting the pathological complete response (pCR) to NAC in patients with early breast cancer. A total of 74 patients underwent PET/MRI, mammography (MG), including tomosynthesis, and ultrasound (US) after NAC. The complete response was predicted using each modality and these outcomes were compared accordingly. In terms of PET/MRI, complete response (CR) was defined as the disappearance of 18F-fluorodeoxyglucose uptake and the absence of enhanced lesions with contrast enhanced MRI. In MG and US, undetectable lesions were considered as CR. The background and tumor characteristics of patients were also analyzed between the pCR and non-pCR cases. Overall, 18 (24.3%) of the 74 patients achieved pCR. The overall sensitivity and specificity of PET/MRI were 72.2 and 78.6%, respectively. Both the sensitivity in hormone receptor (HR)-positive cases and the specificity in HR-negative cases were 100%. HR-negative and human epidermal growth factor receptor 2 (HER2)-positive cases demonstrated a significant association with pCR compared with HR-positive cases and triple negative cases (P=0.017). Furthermore, patients with 'mass' type lesions evaluated by MRI before NAC experienced pCR with a higher frequency than those with 'non-mass' type lesions. There was a statistically significant difference between the two groups (P=0.018). In conclusion, PET/MRI is a different diagnostic approach that utilizes a multi-modality system. It demonstrates reasonable diagnostic accuracies of the responses of NAC with reference to hormonal subtypes in breast cancer.
RESUMO
BACKGROUND: A strategy for maintaining and/or improving cardiorespiratory fitness (CRF) in the growing population of cancer survivors is of major clinical importance, especially in the COVID-19 era. The effect of unsupervised high-intensity interval training (HIIT) on increasing CRF in breast cancer survivors is unknown. PURPOSE: The purpose of this study was to determine whether the newly developed habit-B programme, which involves home-based smartphone-supported HIIT using body weight exercises, improves CRF in early-stage breast cancer survivors. METHODS: This single-centre, 12-week, parallel-group, single-blind, randomised controlled trial involved 50 women with stage I-IIa breast cancer, aged 20-59 years, who had completed initial treatment except for hormone therapy. Participants were randomised to either the exercise or control group. The primary outcome was the 12-week change in peak oxygen uptake [Formula: see text]. Other outcomes included muscle strength, 6 min walk test, resting heart rate, physical activity, fatigue, safety and quality of life. RESULTS: The change in [Formula: see text] and leg strength increased significantly in the exercise group compared with the control group (p<0.01). Changes in other outcomes were not significantly different between the groups. CONCLUSION: A home-based HIIT intervention can lead to improve CRF and muscle strength in early-stage breast cancer survivors.